Abstract

OBJECTIVE Previous studies have demonstrated that mice fed a high-fat diet (HFD) develop insulin resistance with proinflammatory macrophage
infiltration into white adipose tissue. Concomitantly, adipocytes undergo programmed cell death with the loss of the adipocyte-specific
lipid droplet protein perilipin, and the dead/dying adipocytes are surrounded by macrophages that are organized into crown-like
structures. This study investigated whether adipocyte cell death provides the driving signal for macrophage inflammation or
if inflammation induces adipocyte cell death.

RESEARCH DESIGN AND METHODS Two knockout mouse models were used: granulocyte/monocyte-colony stimulating factor (GM-CSF)–null mice that are protected
against HFD-induced adipose tissue inflammation and cyclophilin D (CyP-D)–null mice that are protected against adipocyte cell
death. Mice were fed for 4–14 weeks with a 60% HFD, and different markers of cell death and inflammation were analyzed.